Underestimated associated features in CMT neuropathies: clinical indicators for the causative gene?

Brain and Behavior - Tập 6 Số 4 - 2016
Friederike Werheid1,2, Hamid Azzedine2, Eva Zwerenz1,2, Ahmet Bozkurt3,4, Marcus J. Moeller5, Lilian Tsai‐Wei Lin1,2, Michael Mull6, Martin Häusler7, Jörg B. Schulz1,8, Joachim Weis2, Kristl G. Claeys1,9,2
1Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany
2Institute of Neuropathology, University Hospital RWTH Aachen, Aachen, Germany
3Department of Plastic & Aesthetic, Reconstructive & Hand Surgery Center for Reconstructive Microsurgery and Peripheral Nerve Surgery (ZEMPEN) Agaplesion Markus Hospital Frankfurt am Main Germany
4Department of Plastic and Reconstructive Surgery, Hand Surgery-Burn Center, University Hospital RWTH Aachen, Aachen, Germany
5Section Immunology and Nephrology, Department of Internal Medicine, University Hospital RWTH Aachen, Aachen, Germany
6Department of Neuroradiology, University Hospital RWTH Aachen, Aachen, Germany
7Division of Neuropediatrics and Social Pediatrics, Department of Pediatrics, University Hospital RWTH Aachen, Aachen, Germany
8JARA Translational Brain Medicine, Aachen, Germany
9Department of Neurology, University Hospitals Leuven and University of Leuven (KU Leuven), Leuven, Belgium

Tóm tắt

AbstractIntroductionCharcot–Marie–Tooth neuropathy (CMT) is a genetically heterogeneous group of peripheral neuropathies. In addition to the classical clinical phenotype, additional features can occur.MethodsWe studied a wide range of additional features in a cohort of 49 genetically confirmed CMT patients and performed a systematic literature revision.ResultsPatients harbored a PMP22 gene alteration (n = 28) or a mutation in MPZ (n = 11), GJB1 (n = 4), LITAF (n = 2), MFN2 (n = 2), INF2 (n = 1), NEFL (n = 1). We identified four novel mutations (3 MPZ, 1 GJB1). A total of 88% presented at least one additional feature. In MPZ patients, we detected hypertrophic nerve roots in 3/4 cases that underwent spinal MRI, and pupillary abnormalities in 27%. In our cohort, restless legs syndrome (RLS) was present in 18%. We describe for the first time RLS associated with LITAF or MFN2 and predominant upper limb involvement with LITAF. Cold‐induced hand cramps occurred in 10% (PMP22, MPZ, MFN2), and autonomous nervous system involvement in 18% (PMP22, MPZ, LITAF, MFN2). RLS and respiratory insufficiency were mostly associated with severe neuropathy, and pupillary abnormalities with mild to moderate neuropathy.ConclusionsIn CMT patients, additional features occur frequently. Some of them might be helpful in orienting genetic diagnosis. Our data broaden the clinical spectrum and genotype–phenotype associations with CMT.

Từ khóa


Tài liệu tham khảo

Ananth U. Athena Diagnostics Inc. 1999. Personal data.http://www.molgen.ua.ac.be/cmtmutations/Mutations/Mutations.cfm

10.1212/WNL.12.10.712

Azzedine H., 2012, Molecular genetics of charcot‐marie‐tooth disease: from genes to genomes, Mol. Syndromol., 3, 204, 10.1159/000343487

10.1007/s00415-009-5390-1

10.1136/jnnp-2013-305296

10.1007/s004390050442

10.1056/NEJMoa1109122

10.1212/WNL.52.4.890

Cellerini M., 2000, MR imaging of the cauda equina in hereditary motor sensory neuropathies: correlations with sural nerve biopsy, AJNR Am. J. Neuroradiol., 21, 1793

10.1016/0092-8674(93)90058-X

10.1093/brain/awl174

Davis C. J., 1978, The peroneal muscular atrophy syndrome: clinical, genetic, electrophysiological and nerve biopsy studies. I. Clinical, genetic and electrophysiological findings and classification, J. Genet. Hum., 26, 311

10.1093/brain/122.2.281

10.1002/mus.20034

10.1016/j.nmd.2006.01.006

10.1212/WNL.47.3.761

10.1016/j.nmd.2009.05.006

10.1136/jnnp.59.2.189

10.1093/brain/103.2.259

10.1212/01.wnl.0000336341.72621.db

10.1093/brain/awg012

10.1002/mds.870100103

Kleopa K. A., 2002, Conus medulla‐cauda compression from nerve root hypertrophy in a child with Dejerine‐Sottas syndrome: improvement with laminectomy and duraplasty. Case report, J. Neurosurg., 97, 244

10.1016/0092-8674(91)90613-4

10.1212/01.wnl.0000436615.58705.c9

10.1016/j.nmd.2009.09.004

10.1086/302962

10.1111/j.1529-8027.2011.00350.x

10.1002/humu.10134

10.1186/1750-1172-9-38

10.1016/0960-8966(91)90055-W

10.1111/jns.12106

10.1038/nrneurol.2013.179

10.1002/mds.1209

Schröder J. M.2001.Pathology of peripheral nerves. An atlas of structural and molecular pathological changes.

10.1007/s00415-002-0810-5

10.1111/j.1399-0004.1974.tb00638.x

10.1016/S1388-2457(03)00159-7

10.1016/S0960-8966(02)00021-4

10.1007/s00415-013-7021-0

10.1093/brain/85.2.251

10.1016/j.expneurol.2012.01.010

10.3390/genes5010013

10.1093/brain/awl126

10.1212/WNL.59.5.767

10.5414/NP300468

10.1038/ng1341

Thông tin
Thông tin xuất bản

Brain and Behavior

Tập 6 Số 4

Thông tin tác giả